Category: piperazines

Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin α_IIbβ₃ was written by Krysko, Andrei A.;Kornylov, Alexander Yu.;Polishchuk, Pavel G.;Samoylenko, Georgiy V.;Krysko, Olga L.;Kabanova, Tatyana A.;Kravtsov, Victor Ch.;Kabanov, Vladimir M.;Wicher, Barbara;Andronati, Sergei A.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2016.Reference of 162046-66-4 This article mentions the following:

A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small mol. compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α_IIbβ₃ integrin in a suspension of washed human platelets. The key α_IIbβ₃ protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Reference of 162046-66-4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Reference of 162046-66-4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

N,N’-Bisoxalamides Enhance the Catalytic Activity in Cu-Catalyzed Coupling of (Hetero)Aryl Bromides with Anilines and Secondary Amines was written by Bhunia, Subhajit;Kumar, S. Vijay;Ma, Dawei. And the article was included in Journal of Organic Chemistry in 2017.Application of 780705-64-8 This article mentions the following:

N,N’-Bis(furan-2-ylmethyl)oxalamide (BFMO), an inexpensive and conveniently available bidentate ligand, is very effective for promoting Cu-catalyzed N-arylation of anilines and cyclic secondary amines. The method enables coupling of a broad range of (hetero)aryl bromides with various (hetero)aryl amines and cyclic secondary amines at 0.5-5 mol % catalyst loadings at relatively low temperatures For coupling with more sterically hindered acyclic secondary amines, using N,N’-bis(2,4,6-trimethoxyphenyl)oxalamide (BTMPO) as a ligand gives the better results. Addnl., high selectivity is achieved in CuI/BFMO-catalyzed direct monoarylation of piperazine with (hetero)aryl bromides to afford pharmaceutically important building blocks. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Application of 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Application of 780705-64-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Antibacterial derivatives of 8-alkyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acids. II. 2-Piperazinyl and 2-(4-alkylpiperazinyl) derivatives was written by Pesson, M.;Antoine, M.;Chabassier, S.;Geiger, S.;Girard, P.;Richer, D.;De Lajudie, P.;Horvath, E.;Leriche, B.;Patte, S.. And the article was included in European Journal of Medicinal Chemistry in 1974.Name: 1-Propylpiperazine This article mentions the following:

Piperazinylpyridopyrimidines I (R = Me, Et, CH2CH2OMe, tetrahydropyranyloxyethyl, CH2CH2OH; R1 = Et; R2 = Me, Et, Pr, allyl, Bu, CH2CH2OH, CH2CH2OMe, CH2CN, CH2CO2Et) were prepared by aminating chloropyridopyrimidines II and were hydrolyzed to acids I (R1 = H). I (R2 = H) were similarly prepared via I (R2 = CHO). I (R1 = H) are bactericidal and their activity is discussed relative to R and R2. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Name: 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Name: 1-Propylpiperazine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Identification of a 5-HT₄ receptor antagonist clinical candidate through side-chain modification was written by Clark, Robin D.;Jahangir, Alam;Alam, Muzaffar;Rocha, Cynthia;Lin, Lin;Bjorner, Bodil;Nguyen, Khanh;Grady, Carole;Williams, Timothy J.;Stepan, George;Tang, Hai Ming;Ford, Anthony P. D. W.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2005.Quality Control of 1-Propylpiperazine This article mentions the following:

Replacement of the N-Bu side-chain of lead 5-HT₄ receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (I), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Quality Control of 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Quality Control of 1-Propylpiperazine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of 1,4-Dihydroxy-2-naphthoate Prenyltransferase Inhibitors: New Drug Leads for Multidrug-Resistant Gram-Positive Pathogens was written by Kurosu, Michio;Narayanasamy, Prabagaran;Biswas, Kallolmay;Dhiman, Rakesh;Crick, Dean C.. And the article was included in Journal of Medicinal Chemistry in 2007.Application of 21867-64-1 This article mentions the following:

Since utilization of menaquinone in the electron transport system is a characteristic of Gram-pos. organisms, the 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) inhibitors (I) and (II) act as selective antibacterial agents against organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), and Mycobacterium spp. Growth of drug-resistant Gram-pos. organisms was sensitive to the MenA inhibitors, indicating that menaquinone synthesis is a valid new drug target in Gram-pos. organisms. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Application of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Application of 21867-64-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine (GSK962040), the First Small Molecule Motilin Receptor Agonist Clinical Candidate was written by Westaway, Susan M.;Brown, Samantha L.;Fell, Stephen C. M.;Johnson, Christopher N.;MacPherson, David T.;Mitchell, Darren J.;Myatt, James W.;Stanway, Steven J.;Seal, Jon T.;Stemp, Geoffrey;Thompson, Mervyn;Lawless, Kirk;McKay, Fiona;Muir, Alison I.;Barford, Jonathan M.;Cluff, Chermaine;Mahmood, Sadhia R.;Matthews, Kim L.;Mohamed, Shiyam;Smith, Beverley;Stevens, Alexander J.;Bolton, Victoria J.;Jarvie, Emma M.;Sanger, Gareth J.. And the article was included in Journal of Medicinal Chemistry in 2009.Category: piperazines This article mentions the following:

N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine 12 (GSK962040) is a novel small mol. motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-2-methylpiperazine (cas: 923565-99-5Category: piperazines).

(R)-1-Cbz-2-methylpiperazine (cas: 923565-99-5) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer was written by Han, Xin;Zhao, Lijie;Xiang, Weiguo;Qin, Chong;Miao, Bukeyan;McEachern, Donna;Wang, Yu;Metwally, Hoda;Wang, Lu;Matvekas, Aleksas;Wen, Bo;Sun, Duxin;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C16H22N2O4 This article mentions the following:

Proteolysis targeting chimera (PROTAC) small-mol. degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 (I) being the best compound ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Synthetic Route of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125â€?30 °C. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Synthetic Route of C16H22N2O4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Optimization of a Series of RIPK2 PROTACs was written by Miah, Afjal H.;Smith, Ian E. D.;Rackham, Mark;Mares, Alina;Thawani, Aditya R.;Nagilla, Rakesh;Haile, Pamela A.;Votta, Bartholomew J.;Gordon, Laurie J.;Watt, Gillian;Denyer, Jane;Fisher, Don T.;Dace, Phoebe;Giffen, Paul;Goncalves, Andrea;Churcher, Ian;Scott-Stevens, Paul;Harling, John D.. And the article was included in Journal of Medicinal Chemistry in 2021.Computed Properties of C13H18N2O2 This article mentions the following:

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is an important kinase of the innate immune system. Herein, we describe the optimization of a series of RIPK2 PROTACs which recruit members of the inhibitor of apoptosis (IAP) family of E3 ligases. Our PROTAC optimization strategy focused on reducing the lipophilicity of the early lead which resulted in the identification of analogs with improved solubility and increased human and rat microsomal stability. We identified a range of IAP binders that were successfully incorporated into potent RIPK2 PROTACs with attractive pharmacokinetic profiles. Compound 20 possessed the best overall profile with good solubility, potent degradation of RIPK2, and associated inhibition of TNFα release. A proof-of-concept study utilizing a slow release matrix demonstrated the feasibility of a long-acting parenteral formulation with >1 mo duration. This represents an attractive alternative dosing paradigm to oral delivery, especially for chronic diseases where compliance can be challenging. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5Computed Properties of C13H18N2O2).

(R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Computed Properties of C13H18N2O2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Synthesis of substituted 2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]diazepine-7-sulfamides was written by Filimonov, S. I.;Kravchenko, D. V.;Khakhina, M. Yu.;Dorogov, M. V.;Tkachenko, S. E.;Ivashchenko, A. V.. And the article was included in Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya in 2005.Product Details of 21867-64-1 This article mentions the following:

Liquid-phase parallel synthesis of a combinatorial library of 320 2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-sulfonamides I (R¹, R² = H, Me; R³R⁴N = primary or secondary aliphatic, cycloaliphatic, aromatic or heterocyclic amine) was carried out by chlorosulfonylation of the corresponding benzodiazepines followed by reaction with primary and secondary amines. The pharmacol. important parameters of some of these compounds (mol. weight, lipophilicity and number of hydrogen bond donor and acceptors) have been calculated In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Product Details of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Product Details of 21867-64-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2) was written by Tan, Li;Nomanbhoy, Tyzoon;Gurbani, Deepak;Patricelli, Matthew;Hunter, John;Geng, Jiefei;Herhaus, Lina;Zhang, Jianming;Pauls, Eduardo;Ham, Youngjin;Choi, Hwan Geun;Xie, Ting;Deng, Xianming;Buhrlage, Sara J.;Sim, Taebo;Cohen, Philip;Sapkota, Gopal;Westover, Kenneth D.;Gray, Nathanael S.. And the article was included in Journal of Medicinal Chemistry in 2015.Application In Synthesis of 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

The authors developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacol. well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure-activity relationship (SAR) resulted in the identification effect two potent dual TAK1 and MAP4K2 inhibitors such as I as well as two MAP4K2 selective inhibitors such as II. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacol. studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Application In Synthesis of 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Application In Synthesis of 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics